2. Are USP Reference Standards suitable for applications not specified in the USP-NF publication and other USP compendia?

USP Reference Standards are intended only for use in analytical or laboratory applications as specified in USP compendia. It may be possible to use a USP Reference Standard in other compendial or quality assessment applications; however, it is the responsibility of the user to determine the suitability of the USP Reference Standard for these non-USP compendial purposes. View USP’s policy statement on USP Reference Standard’s Uses and Applications.

USP’s Reference Standards are considered primary standards, except for certain biological USP Reference Standards with units of activity that are established against and traceable to the World Health Organization International Standards. USP does not develop secondary reference standards against its own primary reference standards. USP does not provide guidance on the qualification or use of such secondary reference standards. For questions about the use of primary vs. secondary reference standards and implications for compliance, users are advised to consult with the regulatory authority where their products are marketed for guidance. View USP’s policy statement on USP Reference Standard’s Uses and Applications.

False

4. Can a standard that has been qualified in my laboratory be used in place of a USP Reference Standard?

A USP Reference Standard, where explicitly mentioned in an official USP compendial monograph, is considered to be part of the official method. In the event of a dispute, it is the USP monograph with its associated USP Reference Standard(s) which determines compliance. Use of secondary standards is up to the user to determine. USP cannot comment on the use of a secondary standard in place of the USP Reference Standard (primary standard) specified in a USP compendial monograph. View USP’s policy statement on USP Reference Standard’s Uses and Applications.

False

5. Do USP Reference Standards require any special preparation before use?

All available instructions for use are provided in a USP Reference Standard’s associates USP compendial application(s), the label of the USP Reference Standard and in its USP Certificate, if available. Some lots can be used as–is but others may require drying before use or a correction with a concurrent moisture or Loss on Drying determination. Additional information on special preparation requirements for USP Reference Standards may be found in General Chapter <11> USP Reference Standards and the USP Reference Standard’s associated USP compendial methods. See Use and Storage for more details.

Availability and Validity

True

7. What happens if a new USP Reference Standard that is specified in a USP compendial monograph is not yet available for purchase?

As per Section 5.80 of the General Notices in the USP-NF publication, if any new USP or NF written standard requires the use of a new USP Reference Standard that is not yet available for purchase, that portion of the standard containing the requirement shall not be official until the specified USP reference material is available. This rule does not apply to already existing USP Reference Standards that are on backorder; it is only applicable to never before sold USP Reference Standards.

To learn when a new USP Reference Standard becomes available for the first time, use the New Reference Standards Release Notification Service. This service is not available for the release of back-ordered products or lot changeovers. To receive a monthly list of lot changeovers, please subscribe to our free monthly Email Notice.

False

8. What happens if a USP Reference Standard is on back order?

The availability of USP Reference Standards is generally better than 99 percent. USP strives to plan ahead to replace depleted lots in a timely manner. However, despite our best efforts, some USP Reference Standards might occasionally be out of stock temporarily. Contact Reference Standards Technical Service (rstech@usp.org) to find out when the specific USP Reference Standard you are looking for might become available again. You can also frequently check the product listings in USP's online store which are updated on a daily basis or sign up for our free monthly Email Notice which will keep you informed about USP Reference Standards that become available.

You can place an order for USP Reference Standards that are currently out of stock. Products that become available within 30 days of your order will be shipped to you automatically. If the product becomes available after 30 days, USP will send you a Notice of Availability to get your confirmation before shipping the order.

False

9. Are the impurities listed in a table of a specific USP compendial monograph and other required chemicals and reagents available from USP?

All USP Reference Standards that are required to carry out the tests within a specific monograph will be provided in a list at the end of a monograph. The Reference Standards are written as "USP RS." Other chemicals, reagents, impurities, etc. that are listed in a monograph or General Chapter are not available as USP Reference Standards.

False

10. What is USP’s policy on Product Withdrawals?

If a product is determined by USP to no longer meet the USP compendial requirements, USP will notify customers who purchased the product in the last 12 months that it is being withdrawn. USP recommends referring to the online USP store and the USP Reference Standards Catalog prior to using a USP Reference Standard to make sure the specific lot is valid for use. These sources are updated on a daily basis.

False

11. How do I determine if a USP Reference Standard is still valid for use or has expired?

With the exception of USP Prednisone Tablets RS catalog #1559505, current lots of USP Reference Standards do not have valid use dates (expiration dates). As long as a lot is listed as being the “current lot,” it is valid and suitable for use. Once a current lot is depleted, it becomes the “previous lot.” At this time a valid use date is assigned, which is typically 3-12 months from the date of depletion.

Technical Data Sheets (USP Certificates, Safety Data Sheets, etc.)

USP does not provide COAs. USP does provide USP Certificates for most USP Reference Standards (RS). USP Certificates do not completely describe the test results obtained during evaluation. Rather, they are issued to provide customers with information such as a hard copy of the USP RS label text, molecular information, typical chromatograms (limited cases), and additional use/handling information that may not be contained on the RS label. View USP’s policy statement on USP Certificates and Assigned Values.

False

13. Where can I find the USP Certificate for a USP Reference Standard?

14. Where can I find the Safety Data Sheet (SDS) for a USP Reference Standard?

SDSs are available online for all USP Reference Standards at www.usp.org/sds. They can also be viewed by clicking on the Product Description in the online USP store. This product page in the online store can also be accessed by clicking on the catalog number of the product in the USP Reference Standards Catalog.

False

15. Are Safety Data Sheets (SDSs) available in different formats and languages?

SDSs are not available in additional formats and languages. It is the responsibility of the importer to provide SDSs in the required format, if different.

False

16. Is the Safety Data Sheet (SDS) available on the USP website the most up-to-date version?

The SDS's posted on our web site are the most recently updated versions. The U.S. OSHA Hazard Communication Standard does not specify a specific time frame beyond which SDS information is to be considered unacceptable.

False

17. Why does the Safety Data Sheet (SDS) of a particular USP Reference Standard not meet the U.S. Occupational Safety and Health Administration (OSHA) standard (HazCom2012) requirements that went into effect on May 25, 2012?

OSHA published the HazCom2012 requirements to bring U.S. SDSs in line with the Globally Harmonized System of Classification and Labeling of Chemicals (GHS). These requirements are applicable only to hazardous materials as defined by HazCom2012. USP revised all applicable SDSs to comply with these new OSHA regulations. The regulatory deadline for implementation was June 1, 2015.

False

18. Is the information on the Safety Data Sheet (SDS) of a USP Reference Standard obtained in USP laboratories?

Testing is not required by the U.S. Occupational Safety and Health Administration (OSHA) as the basis for a safety evaluation or an SDS. USP relies on published and supplier data in conformance with OSHA regulations. SDS’s should not be used as Certificates of Analysis. USP Reference Standards are intended only for use in their associated USP compendial applications. Any use beyond these applications is the responsibility of the user. USP Reference Standards are not for human and animal use.

There are a limited number of USP Reference Standards that have an available Typical Chromatogram. If provided, the Typical Chromatogram is included in the USP Certificate. Details that are not included on the chromatogram are confidential and not available. IR spectra are not available for any USP Reference Standards.

False

20. Where can I find specific test results for a USP Reference Standard?

All information required for the official use of a USP Reference Standard is provided in the associated USP compendial monograph(s) and/or General Chapter(s), the label of the USP Reference Standard, and on its USP Certificate, if available. Due to legal and scientific reasons, test results and data that are not included in these sources cannot be shared.

False

Assigned Value (Purity/Potency)

True

21. Where can I find the purity/potency value of a USP Reference Standard?

In most cases, the assigned value can be found on the label of a USP Reference Standard. If a value is not provided on the label or USP Certificate and the Reference Standard has a quantitative USP compendial application, a value of 100.0% is used. This applies only to USP Reference Standards developed for quantitative use in USP compendial procedures. The value is not applicable for USP Reference Standards developed only for qualitative USP compendial use(s). Please refer to a USP Reference Standard’s USP compendial application(s) to determine if the RS is used qualitatively and/or quantitatively. View USP’s policy statement on USP Certificates and Assigned Values.

False

22. How is the assigned value of a USP Reference Standard calculated?

The method of choice in computing the assigned value of a USP Reference Standard is a mass balance analysis using independently determined components such as moisture, solvent residues, inorganic residues, chromatographic impurities and ion content. The mass balance equation used is confidential and cannot be shared due to legal and scientific reasons. The assay results against a previous lot or against another validated standard and the results of the functional group analysis are for confirmatory purposes only.

USP uses the mass balance approach as this provides a more precise determination of the assigned value than assaying versus a previous lot. The assaying versus a previous lot approach inherently causes greater variability and less precision due to the variability of the previous lot being incorporated into the overall variability of the lot under evaluation. The mass balance approach also results in higher accuracy.

Exceptions to the mass balance approach include many biological Reference Standards, especially those which define the Unit of Activity. A value is not assigned to Reference Standards having only qualitative USP compendial uses.

False

23. Why has the basis (e.g. dried, anhydrous) of the assigned value changed from one lot to another?

Assigned values, including their basis, are lot-specific and may change from one lot to another. For the convenience of our customer, USP is labeling a USP Reference Standard on the "as is basis" whenever possible. It is the preferred option and is selected whenever valid data indicates that the volatiles content is constant over time. The change to "as is" will not affect the USP compendial use of a USP Reference Standard.

False

24. How do USP Units convert to International Units?

Refer to the USP compendial monograph of a specific material for available information on the Unit of measurement used by USP for purity, potency, etc. of a specific compound. Conversion factors for USP Units may not be available as USP does not regularly use International Units. If a conversion is not included in the USP compendial monograph, it is not available from USP.

Please click here to read USP’s statement on the Heparin Potency Unit Assignment and Harmonization with the International Standard for Unfractionated Heparin.

False

Label Format and Content

True

25. Do USP Reference Standard labels meet the requirements put into law by the U.S. Occupational Safety and Health Administration (OSHA) HazCom2012 standards?

USP has transitioned to revised label formats to meet the labeling requirements of the HazCom2012 standard. The required label elements are signal words, hazard statements, precautionary statements & pictograms, product identifier, and supplier identification. All elements except the precautionary statements are visible on the outside label of a USP Reference Standard vial. The precautionary statements can be found under the wrap-label.

False

26. Why is a USP Reference Standard over-labeled?

Some USP Reference Standards have a wrap-label with all label elements required by HazCom2012 placed over the original labels. The updated wrap-label includes the same information as the label in the old format with the addition of precautionary statements & pictograms, and the updated language for signal words and hazard statements. These products will include a statement on the label indicating that they are intentionally over-labeled. Please refer to FAQ #25 for more details about the new label format.

False

27. What does “AS” stand for on the label of a USP Reference Standard?

AS stands for Authentic Substance. Authentic Substances were developed by USP as a service primarily to analytical, clinical, pharmaceutical, and research laboratories. Although USP no longer releases new lots labeled as Authentic Substances, you may still receive a lot released prior to this change. Such substances may be used for identification, method development, evaluation of method performance, or other applications as found suitable and validated by the user. AS Reference Standards do not have USP applications in monographs or other compendial standards. All available information can be found on the label of the AS Reference Standard. No additional data is publicly available.

False

28. Why does the catalog number on my Reference Standard not match the catalog number in the online USP store and the USP Reference Standards Catalog, and will that affect its USP compendial use(s)?

USP changed the numbering system for all USP Reference Standard catalog numbers. A “1” was added as the first digit to the existing catalog number and an additional digit was added to the end if the existing number was only 5 digits. If there was a hyphen in the existing catalog number followed by a sixth digit, the hyphen was removed. All catalog numbers are now 7 digits in length. Please see the table below for examples.

Product Description

Old Catalog No.

New Catalog No.

Hypromellose Phthalate (100 mg)

33530

1335304

Bumetanide Related Compound B (25 mg)

07833

1078336

There are still lots that were labeled prior to this change in distribution, so the catalog number on the label will be the old catalog number. Whether the catalog number printed on the USP RS label is from the old or new numbering system, it has no bearing on the potency, stability, or suitability for use of the USP RS. USP monitors products in our inventory on a regular basis in the Continued Suitability for Use (CSU) Program.

False

Shipping and Storage

True

29. What is the storage condition for a USP Reference Standard?

The storage condition for an unopened USP Reference Standard can typically be found on the container label. Storage conditions are no longer provided in the Safety Data Sheets (SDSs). Instead, the SDS refers users to the USP Reference Standard label. Storage conditions are lot-specific and may change from one lot to another. If no specific directions or limitations are provided on the USP Reference Standard label, the conditions of storage shall include storage at room temperature and protection from moisture, light, freezing, and excessive heat. Refer to General Chapter <659> Packaging and Storage Requirements in the USP-NF publication for definitions of storage and handling terms. See Use and Storage for more details. View USP’s policy statement on Shipping and Storage Conditions of USP Reference Standards.

False

30. Can USP Reference Standards be stored after opening for future use?

USP generally provides enough material for multiple preparations. Any unused portions remaining after the container has been opened should be carefully stored in accordance with prudent laboratory procedures. Many variables are outside of the control of USP. Therefore, USP makes no warranties concerning the continued suitability of previously opened USP Reference Standards. Decisions concerning the proper use of previously opened USP Reference Standards are the responsibility of the user. View USP’s policy statement on Shipping and Storage Conditions of USP Reference Standards.

False

31. Why is the storage condition of a USP Reference Standard different from the storage condition provided in a USP compendial monograph?

The storage condition of a USP Reference Standard is determined based on the recommendation from the material’s supplier/manufacturer. Data obtained during the collaborative study of a lot and historic data are also considered. The provided storage condition of a USP Reference Standard is intended to preserve the integrity of the Reference Standard for the duration of its use as an RS. The storage condition in a USP compendial monograph is based on the recommendation of the monograph’s sponsor. The storage condition provided in a monograph is for the article of commerce.

False

32. Can a USP Reference Standard be stored at a different temperature other than what is provided on the label? Is the material still suitable for use if a temperature excursion occurs?

The provided storage condition is also how USP stores the specific product. Continued Suitability for Use (CSU) testing is performed on the material stored as per its label. For this reason, we do not have data to support the continued suitability of the material when stored at an alternate temperature. It is the responsibility of the user to determine if a material remains suitable for use when handled differently than the provided instructions. USP also cannot comment on the potential effect of temperature excursions that occurred in the storage location of a USP Reference Standard. The user should consult their own internal policies & SOP’s and use their best scientific judgment to make the decision on whether or not to use the material(s) if an excursion occurs.

False

33. Do USP Reference Standards require special shipping?

USP Reference Standards are not customarily shipped on ice or under refrigerated conditions, despite their labeled storage condition. Shipping conditions are determined based on the stability information for individual USP Reference Standards and transit times. If scientific evidence suggests the need to ship a USP Reference Standard on ice or dry ice, USP will do so. For these products, a statement that a cold shipment is required will be included in the Product Description [e.g. Endotoxin (10,000 USP Endotoxin Units) (COLD SHIPMENT REQUIRED)]. View USP’s policy statement on Shipping and Storage Conditions of USP Reference Standards.

Shipping on ice or dry ice is available for all USP Reference Standards on request and for an extra charge - Call USP Customer Service at 1-800-227-8772 (U.S. and Canada), +1-301-881-0666, or 00-800-4875-5555 (Select Europe) for details.